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Catecholamine induced cardiac hypertrophy
Q Tang1, P B Taylor, R K Helbing
1Department of Biological Sciences, University of Windsor, Ontario.
Insights
Isoproterenol treatment induced cardiac hypertrophy in rats, increasing heart weight and enhancing RNA polymerase activity and chromatin template function in both myocytes and non-myocytes during early stages. These changes promote RNA synthesis in hypertrophied hearts.
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- Biochemistry
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- Understanding the molecular mechanisms driving cardiac hypertrophy is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of RNA polymerase activity and chromatin template function in the early stages of isoproterenol-induced cardiac hypertrophy.
- To elucidate the cellular and molecular changes in myocytes and non-myocytes during the development of cardiac hypertrophy.
Main Methods:
- Cardiac hypertrophy was induced in Wistar rats using isoproterenol injections.
- RNA polymerase activity was measured in isolated myocyte and nonmyocyte nuclei.
- Chromatin template function was assessed by enzyme binding capacity and DNA fragmentation analysis.
Main Results:
- Isoproterenol treatment led to significant increases in heart weight and left ventricular pressure development.
- RNA polymerase activity and chromatin template function were enhanced in both myocyte and nonmyocyte fractions during early hypertrophy (1-4 days).
- Hypertrophied heart chromatin exhibited increased enzyme binding capacity and reduced DNA fragmentation.
Conclusions:
- Enhanced RNA polymerase activity and chromatin template function play a coordinated role in RNA synthesis during early isoproterenol-induced cardiac hypertrophy.
- Alterations in chromatin composition may underlie the increased template activity observed in hypertrophied hearts.
- These findings provide insights into the molecular adaptations of cardiac cells during hypertrophy.
Abstract:
Cardiac hypertrophy was induced in adult female Wistar rats by daily subcutaneous injections of isoproterenol (0.3 mg/kg body weight). Heart weight increased 39% after eight days of treatment. Left ventricular pressure development (positive dP/dt) in hearts four days after hypertrophy induction was significantly increased, while negative dP/dt remained unchanged. RNA polymerase activity in isolated myocyte and nonmyocyte nuclei was stimulated 29 and 23%, respectively 24 h after a single isoproterenol injection. In the myocyte fraction, RNA polymerase activation progressively increased up to four days of treatment and then returned to control values after eight days. In the nonmyocyte nuclear subset, RNA polymerase activity showed no further stimulation and gradually returned to control values after eight days of treatment. Chromatin template function was substantially stimulated in the early stage (one to four days) of hypertrophy in both myocyte and nonmyocyte fractions. Titration of chromatin against a fixed amount of RNA polymerase (5 micrograms) in the presence of rifampicin and heparin showed that less chromatin from hypertrophied hearts was required to saturate the enzyme. These results indicate that both myocyte and nonmyocte chromatin from hypertrophied hearts can support greater enzyme binding than normal chromatin. The alkaline sucrose density centrifugation profile of DNA in myocyte and nonmyocyte chromatin from day 4 hypertrophied hearts was less fragmented. These observations suggest that during the early phase of isoproterenol-induced cardiac hypertrophy, enhanced RNA polymerase activity and chromatin template function play a coordinated role in RNA synthesis. The increased template activity could be due to alterations in chromatin composition which was indicated by the change in their enzyme binding capacity and DNA fragmentation profile.